CAR T Therapy With GCAR1 for Relapsed Alveolar Soft Part Sarcoma

NCT06813417 | Active Not Recruiting Early Phase 1

• 2 other identifiers: CLIC-YYC-GPMB-04HREBA.CC-24-0417
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

A single patient study to determine whether GCAR1 is safe and effective for re-treatment of alveolar soft part sarcoma (ASPS) with GPNMB surface expression that has relapsed and is not responding to usual treatment.

Conditions

Sarcoma; Alveolar Soft Part Sarcoma (ASPS)

Keywords

CAR T; GCAR1

Outcome Measures

Primary Outcomes (1)

• Treatment Response

  The overall response assessment considers the response of the target and non-target lesions and development of new lesions. Response Classification of Target Lesions, CNS lesions and Non-Target Lesions * Complete response (CR): * Partial response (PR): * Progressive disease (PD): * Stable disease (SD):

  Diagnostic imaging (CT and/or MRI) will be performed at baseline (pre-treatment) and then subsequently at 4-6 weeks after GCAR1 infusion, and at 3 months, 6 months, 9 months and 1 year after last infusion to evaluate response to therapy.

Study Arms (1)

GCAR1

EXPERIMENTAL

This is an intrapatient two-dose escalation study. The patient will receive two separate intravenous infusions of cryopreserved, autologous GCAR1, with at least three months (+/- 30 days) between infusions. Both infusions will be preceded by standard lymphodepleting chemotherapy (Fludarabine 40 mg/m2 x 3 days, cyclophosphamide 600 mg/m2 x 2 days) . Dose 1 will be 5.0E6 CAR+ T cells/kg patient body weight, Dose 2 will be 2.5E7 CAR+ T cells/kg patient body weight. Infusions will be intravenous, single infusions.

Biological: GCAR1

Interventions

GCAR1 BIOLOGICAL

GCAR1 is a patient-specific cell therapy product containing a mixture of autologous lymphocytes transduced with a lentiviral vector encoding a chimeric antigen receptor (CAR) targeting GPNMB. The CAR comprises a single-chain variable fragment (scFv) binding domain derived from a fully human GPNMB-specific monoclonal antibody (CDX-011), a CD8 hinge and transmembrane domain, and the CD137 (4-1BB) and CD3 zeta chain intracellular signaling domains. Following infusion, the autologous GPNMB CAR T-cells expressing the genetically engineered anti-GPNMB CAR enable the specific targeting of GPNMB-expressing cells. Upon binding to GPNMB-expressing cells, the CAR transmits T cell activation signals that promote the elimination of target cells through CAR T cell degranulation and the release of cytotoxic molecules. The cellular signal also facilitates CAR T cell proliferation and persistence that may enable prolonged disease control through immunosurveillance3.

GCAR1

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient must provide informed consent
• Adequate organ function, defined as creatinine clearance \>30 ml/min and LVEF \>45%

You may not qualify if:

• Any active uncontrolled infection
• Pregnancy or nursing
• Anti-cancer therapy within 21 calendar days prior to the first dose of lymphodepleting chemotherapy. If subject has received anti-cancer therapy, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy as per the discretion of the Qualified Investigator/Co-Investigator

Sponsors & Collaborators

• University of Calgary: lead
• Alberta Health Services, Calgary: collaborator
• Alberta Precision Laboratories: collaborator

Study Sites (1)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

MeSH Terms

Conditions

Sarcoma; Sarcoma, Alveolar Soft Part

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2025
• First Posted: February 7, 2025
• Study Start: January 30, 2025
• Primary Completion (Estimated): January 30, 2030
• Study Completion (Estimated): January 30, 2030
• Last Updated: April 10, 2025

Record last verified: 2025-01

Locations

CA (1)